Zellweger syndrome (ZS) - also called Cerebrohepatorenal Syndrome, is a rare metabolic disease resulting from disorders of the peroxisome function. What are the causes and symptoms of Zellweger syndrome?

Zellweger syndrome(Zellweger syndrome) is a metabolic disease - the most severe type of peroxisome biogenesis disorders, Zellweger syndrome spectrum (PBD) -ZSS).

Children with Zellweger syndrome most often die before the age of 1.

Disturbances of neuronal migration in the brain, features of craniofacial dysmorphia, significant hypotension, neonatal convulsions and liver dysfunction are characteristic of this syndrome.

The incidence of Zellweger syndrome is estimated at 1 / 50,000 in North America and 1 / 500,000 in Japan. The highest incidence is found in the Saguenay-Lac-St-Jean region of Quebec (approximately 1 / 12,000 births).

Zellweger syndrome: symptoms

The most severe form of peroxisome biogenesis disorder is the cerebrohepatorenal syndrome described in 1964 by Zellweger and named after him.

In 1973, Goldfisher, in a morphological study, showed the absence of peroxisomes in hepatocytes and renal tubular cells in infants with this syndrome.

The characteristics of Zellweger syndrome are:

  • facial and skull dysmorphia: high forehead, Mongolian fold
  • brain development disorders, peripheral nerve myelination disorders, EEG abnormalities
  • deep psychomotor handicap
  • hepatomegaly or enlargement of the liver
  • congenital heart disease
  • renal cystic disease
  • hypospadias
  • calcium deposits in the bone marrow
  • in newborns: flaccidity, convulsions, cataracts, retinopathy, reluctance to suck, cholestasis
  • characteristic "speckling" of the bones visible in x-rays, mainly in the patella (occurs by about 50% of patients with this syndrome)
  • high levels of iron, liver parameters (transaminases), bile acids

Zellweger syndrome: causes

Peroxisomes are organelles found in all human cells, except for mature erythrocytes.

These tiny proteins, with a diameter0.1-1.0 microns were discovered in 1954. They are essential for the development, morphogenesis, differentiation and functioning of the organism, both in such low life forms as fungi, as well as in mammals and humans.

The biogenesis of peroxisomes in humans is related to the function of genes belonging to the PEX group - so far 13 genes of this group have been identified, the products of which are necessary for the formation and construction of these organelles.

Peroxisomes exhibit exceptional morphological and metabolic diversity and a physiological role depending on the organism, stage of development, type of cell and metabolic state of the organism.

Peroxisome membrane has dynamic properties, thus determining the biochemical variability of these organelles and adapting to the metabolic and physiological state of the cell and environmental conditions.

These proteins are most abundant in the cells of the liver and kidneys. More than 50 biochemical reactions have been shown to occur in peroxisomes.

They are classified depending on the biochemical processes in which they participate, incl. on proteins that act as antioxidants, involved in the metabolism of lipids, proteins and amino acids, purines, and the synthesis of glycerol.

Their most important functions are participation in the detoxification of hydrogen peroxide and the metabolism of fatty acids. Errors in the pathways of change lead to diseases manifested by severe clinical symptoms.

Due to the fact that a large part of the reaction is related to the metabolism of lipids, compounds necessary in the formation and functioning of the nervous system, most peroxisome-related diseases are accompanied by symptoms resulting mainly from damage to the nervous system - central and peripheral.

A group of congenital metabolic errors caused by abnormalities in the structure or function of peroxisomes, known asperoxisomal diseases .

The pathogenetic basis of peroxisomal diseases is divided into three groups:

  • diseases associated with a disorder of peroxisome biogenesis (such as Zellweger disease)
  • diseases associated with a single enzyme or protein defect
  • metabolic diseases with concomitant peroxisomal defect

So far, 16 diseases resulting from abnormal peroxisome function have been described, 14 of them are associated with damage to the nervous system.

Other peroxisomal diseases

Neonatal adrenoleukodystrophy , a form of neonatal Refsum's disease, is a milder form of Zellweger syndrome with a longer survival.

Chondrodystrophyrhizomyelic , another disease belonging to the group of peroxisome biogenesis disorders, is characterized only by facial dysmorphism and ossification disorder, shortening of the proximal parts of the limbs and cataracts.

Diseases of the second group, resulting from the mutation of a single enzyme or transport protein, include, among others, adrenoleukodystrophy, classic form of Refsum's disease, chondro rhizomyelic dystrophy, akatalasia, hyperoxaluria.

Diseases of the third group - metabolic diseases with a parallel peroxisomal defect - include such disorders ascontinuous gene syndromeand lethal mitochondrial-peroxisomal defect.

Diagnostics of peroxisomal diseases

Specific biochemical markers are used to diagnose peroxisomal diseases.

In recent years, there has been a rapid development of highly specialized diagnostic techniques and the use of new methods in the study of genetically determined metabolic defects, which makes it possible to detect new peroxisomal defects and to learn about pathomechanisms already known in detail, and in the future may facilitate the development of an effective method of their treatment.

Category:

Genetic diseases